Three areas of investigation are covered in this application. The first of these involves the use of tracer methodology to define the componets of sodium and potassium transport in red cells from uremic patients before and after hemodialysis. These experiments have relevance to the shortened red cell survival which is found in uremic patients. Other studies in uremia relate to the presence of a circulating inhibitor of sodium transport, which exists in uremic dog and man and may play a role in many of the abnormalities of uremia. An animal model will be used to determine whether its appearance can be prevented by adjustments in sodium intake. These studies have the added potential of leading to the development of a new bioassay for the "natriuretic factor" using the red cell transport system. The second group of studies concerns the interrelationship between anions and cations in transmembrane transport. Special attention will be devoted to the mechanisms involved in the enhancement of sodium transport by bicarbonate in human red cells. The third group of studies involves the effect of mechanical stress on red cell transport and metabolism. These studies interdigitate with the experiments relating to the anemia of uremia. The influence of uremia and hemodialysis on the ability of red cells to withstand shearing will be examined and the effect of anion and membrane potential alterations on the ability of red cells to withstand shearing will also be tested.